Phenotypic screening, transcriptional profiling, and comparative genomic analysis of an invasive and non-invasive strain of Candida albicans.
BACKGROUND
Invasion of host tissue by the human fungal pathogen Candida albicans is an important step during the development of candidosis. However, not all C. albicans strains possess the same invasive and virulence properties. For example, the two clinical isolates SC5314 and ATCC10231 differ in their ability to invade host tissue and cause experimental infections. Strain SC5314 is invasive whereas strain ATCC10231 is non-invasive and strongly attenuated in virulence compared to SC5314. In this study we compare the in vitro phenotypic, transcriptional and genomic profiles of these two widely used laboratory strains in order to determine the principal biological and genetic properties responsible for their differential virulence.


RESULTS
In all media tested, the two strains showed the same metabolic flexibility, stress resistance, adhesion properties and hydrolytic enzyme secretion in vitro. However, differences were observed in response to cell-surface disturbing agents and alkaline pH. Furthermore, reduced hyphal formation in strain ATCC10231 under certain conditions correlated with reduced invasive properties in an in vitro invasion assay and a reduced ability to invade epithelial tissue. Despite these diverse phenotypic properties, no substantial genomic differences were detected by comparative genome hybridisation within the open reading frames. However, in vitro transcriptional profiling displayed major differences in the gene expression of these two strains, even under normal in vitro growth conditions.


CONCLUSIONS
Our data suggest that the reason for differential virulence of C. albicans strains is not due to the absence of specific genes, but rather due to differences in the expression, function or activity of common genes.
Thewes
Sascha
S
Division FG16 Mycology, Robert Koch Institute, Berlin, Germany. sascha.thewes@fu-berlin.de
Moran
Gary P
GP
Magee
Beatrice B
BB
Schaller
Martin
M
Sullivan
Derek J
DJ
Hube
Bernhard
B
D000645:Ammonium Sulfate / Q000378:metabolism; D000818:Animals; D002176:Candida albicans / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D002448:Cell Adhesion; D004271:DNA, Fungal / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D005800:Genes, Fungal; D016681:Genome, Fungal; D023281:Genomics / Q000379:methods*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D041681:NIH 3T3 Cells; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames; D010641:Phenotype; D012331:RNA, Fungal / Q000235:genetics; D014158:Transcription, Genetic; D014774:Virulence
D004271:DNA, Fungal; D012331:RNA, Fungal; D000645:Ammonium Sulfate